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1.
Open Forum Infectious Diseases ; 9(Supplement 2):S734-S735, 2022.
Article in English | EMBASE | ID: covidwho-2189885

ABSTRACT

Background. Universities are interactive communities where frequent contacts between individuals occur, increasing the risk of outbreaks of COVID-19. We embarked upon a real-time wastewater (WW) monitoring program across the University of Calgary (UofC) campus measuring WW SARS-CoV-2 burden relative to levels of disease in the broader surrounding community. Figure 1 The colour scheme shows 6 sewer sub-catchments at the University of Calgary. Auto samplers were deployed at 4 sampling nodes within sub-catchments CR and YA (both residence halls), and UCE and UCS (catchments that include several campus buildings). Figure 2 Log10-transformed abundance (i.e., copies per mL) of nucleocapsid gene (i.e., N1) for SARS-CoV-2 for each sampling location during October 2021 - April 2022. Locations denoted by the same letters (A, B, or C) show no statistical difference (p > 0.05) according to the Wilcoxon rank-sum test. The WWTP sample corresponds to a catchment area covering most of Calgary including the university campus, for which sampling locations CR, UCE, UCS, and UCW are defined in Fig. 1. Methods. From October 2021 - April 2022, WW was collected thrice weekly across UofC campus through 4 individual sewer sampling nodes (Fig. 1) using autosamplers (C.E.C. Analytics, CA). Results from these 4 nodes were compared with community monitoring at Calgary's largest WW treatment plant (WWTP), which received WW from surrounding neighborhoods, and also from UofC. Nucleic acid was extracted from WW for RTqPCR quantification of the N1 nucleocapside gene from SARS-CoV-2 genomic RNA. Qualitative (positive samples defined if cycle threshold < 40) and quantitative statistical analyses were performed using R. Results. Levels of SARS-CoV-2 in WW were significantly lower at all campus monitoring sites relative to the WWTP (Wilcoxon rank-sum test p < 0.05;Fig. 2). The proportion of WW samples that were positive for SARS-CoV-2 was significantly higher for WWTP than at least two campus locations (p < 0.05 for Crowsnest Hall and UCE - University way and campus drive) according to Fischer's exact 2-sided test. The proportion of WW samples with positive WW signals were still higher for WWTP than the other two locations, but statistically not significant (p = 0.216). Among campus locations, the buildings in UCE catchment showed much lower N1 signals than other catchments, likely owing to buildings in this catchment primarily being administration and classroom environments, with lower human-to-human contact and less defecation compared to the other 3 catchments, which include residence hall, a dining area, and/or laboratory spaces. Conclusion. Our results show that SARS-CoV-2 RNA shedding in WW at the U of C is significantly lower than the city-wide signal associated with surrounding neighborhoods. Furthermore, we demonstrate that WW testing at well-defined nodes is a sampling strategy for potentially locating specific places where high transmission of infectious disease occurs.

2.
Biochimica Clinica ; 46(3):S18-S19, 2022.
Article in English | EMBASE | ID: covidwho-2167992

ABSTRACT

Introduction: NAAT is still the international reference assay for the diagnosis of Covid-19 due to high sensitivity and specificity;it is able to detect the pathogen even at low viral load, nevertheless a positive PCR result demonstrates the presence of nucleic acid in the sample, but not if it contains an infecting virus;the risk of unnecessarily isolate a person who is no longer infectious and a long TAT can preclude a screening utility. Conversely, immunoassays targeted to detect viral antigens have the potential to fit the requirements for a screening population test. In this study, we evaluated the consistency of results obtained by Maglumi SARS-CoV-2 Ag test in comparison with molecular test. Method(s): 79 positive NAAT nasopharyngeal swabs (NPS) with Ctthreshold cycle (Ct) between 39 and 13 were selected and analysed with MAGLUMI CLIA assay targeted to nucleocapsid SARS-Cov-2 antigen (M) by Snibe Diagnostic. 37 NPS were also analysed with Liaijson XL (L), DiaSorin s.p.a., which is routinary used in our lab. 5 negative NPS were included in the experiment as negative controls. Result(s): all 5 negative NPS were confirmed negative with both CLIA assays. 33 of 79 (41,8%) positive NPS were confirmed positive on M, all these samples had a Ct < 26. The remaining 46 positive NPS, resulting negative on M, had a Ct > 24. Results for 37 NPS tested both with M and L agreed 100%. Conclusion(s): CLIA test demonstrated to be less sensitive to the viral presence than NAAT, in particular M test seems to be able to detect a positivity to SARS-Cov-2 when the viral load is detected at a CT < 24. The grey area, where NAAT and CLIA were not in perfect agreement, seems to be Ct= 24 / 25. In this area M missclassified 67% of positive NPS, but further investigation with a larger number of samples is necessary to confirm this finding. While PCR positivity may persist for several weeks after the onset of the disease and the disappearance of symptoms, Ag tests reach satisfactory sensitivities when infected people are more likely to be contagious;together with the high throughput of the technology, makes them an extremely useful tool for screening population, especially during the pandemic.

3.
Revue Medicale Suisse ; 17(723):234, 2021.
Article in French | EMBASE | ID: covidwho-2146894
4.
New Armenian Medical Journal ; 16(2):14-24, 2022.
Article in English | EMBASE | ID: covidwho-2067786

ABSTRACT

Researches aimed at finding effective means of pathogenic therapy for this viral infection are extremely relevant. Researches of the last three years have established that some human pathogenic coronaviruses - MERS, SARS-CoV and SARS-CoV-2, contain aliphatic polyamines in their structure, which participate in the packaging of genetic material (DNA, RNA), as well as the nucleocapsid. Virus-host cell interactions also provide adhesion processes on the surface of the cytoplasmic membrane of target cells. In the intra-cellular space, aliphatic polyamines actively affect the translation and replication processes of the genetic material and necessary proteins of the virus itself, as well as the formation of daughter viruses. Long-term persistence in the SARS-CoV-2 infected organism is largely due to the absorption of polyamines by corona-virus localized in target cells of the blood and parenchymatous organs. Unfortunately, the above new facts did not serve as a prerequisite for finding effective means of pathogenetic therapy for COVID-19, based on the inhibition of polyamine-dependent processes that ensure long-term persistence of SARS-CoV-2 in the infected organism. We are talking about specific drugs such as alpha-difluoromethylornithine and its ana-logues, which are successfully used in oncology in the complex treatment of malignant neoplasms with the aim of lowering the level of aliphatic polyamines in the affected areas of malignantly transformed organs. We recommend the use of polyamine-free and polyamine-deficient diets for COVID-19 for the first time. In the planned study, we will present tables with food products of animal and vegetable origin, characterized by extremely low content and/or absence of aliphatic polyamines in them. At the same time, food products with a high content of aliphatic polyamines should be excluded from the general list of products recommended for COVID-19 patients. We also recommend the use of a polyamine-deficient diet (with a preventive purpose) during the COVID-19 pandemic to a wide contingent of practically healthy individuals, convalescents, medical staff of specialized infectious disease clinics, as well as family members of SARS-CoV-2 infected patients. Copyright © 2022, Yerevan State Medical University. All rights reserved.

5.
Clinical and Experimental Rheumatology ; 40(10):83, 2022.
Article in English | EMBASE | ID: covidwho-2067780

ABSTRACT

Sjogren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth due to the secretory dysfunction of the lacrimal and salivary glands. In recent years, infectious pathogens have been proved to be associated with SS, including Cytomegalovirus, Coxsackie, EBV, and lymphotropic virus-1 (HTLV-1). Studies suggest that infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an autoimmune response, as evidenced by increased autoantibodies in patients diagnosed with Coronavirus disease 2019 (COVID-19). To investigate the relationship between SARS-CoV-2 and SS, the study was performed by infecting humanized ACE2 mice with SARS-CoV-2. Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) and anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. We detected the viral nucleocapsid protein in mice exocrine glands with significant apoptotic bodies by the acinar cells. Confirmed with clinical data, we also observed the elevation of SS-specific autoantibodies (ANA, anti-SSB/Ro52, and anti-SSA/La) and specific ANA patterns in sera from COVID-19 patients. One unique aspect of SS is the high degree of sexual dimorphism, with women being affected 10-20 times more than men. To determine whether COVID-19 patients exhibited an element of sexual dimorphism in the autoantibody response, we grouped the sera by sex. We found the male patients showed elevated anti-SSA/Ro52 compared to female patients (p=0.0029), and female patients had more diverse ANA patterns. Lastly, monoclonal antibodies isolated from recovered patients using singlecell antibody nanowells technology were shown to recognize the nuclear antigens. Overall, by observing SS-like phenotypes in mouse models and patients, our study confirms a direct pathogenic role of SARS-CoV-2 in SS.

6.
Mediterranean Journal of Infection, Microbes and Antimicrobials ; 11(1) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2066934

ABSTRACT

Introduction: Severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) antibodies are produced in persons who have been infected by the virus or have received the vaccine. Many features of these antibodies, including their dynamics and neutralization capacities, are still unclear. Understanding the immune response of the host is very important for the development of appropriate treatment methods, vaccines, and epidemiological control strategies. The present study aimed to monitor the change in antibody levels over time in individuals diagnosed with SARSCoV- 2 infections and to determine their neutralization capacity. Material(s) and Method(s): Anti-nucleocapsid and anti-spike antibody titers were measured using different kits on monthly obtained serum samples of patients of patients with SARS-CoV-2 infection. The neutralizing antibodies were evaluated using a microneutralization assay. Result(s): A total of 134 serum samples taken from 43 patients with a mild-moderate disease course were analyzed. Anti-spike antibody positivity was detected on day seven at the earliest and day 334 at the latest following a positive polymerase chain reaction (PCR) test. The mean antibody levels were observed to increase gradually to a peak after three months, and then started to decrease after month six. Anti-nucleocapsid IgM and IgG antibodies were detected alone or in combination. The highest neutralizing antibody titer was 1/80 in the first month, which was seen to drop below 1/10 after four months. Conclusion(s): The combined use of kits for the detection of antibodies against different antigens or testing total antibodies would result in a more accurate and earlier detection of the antibodies that start to emerge on the seventh day and decrease six months after SARS-CoV-2 PCR positivity. In addition, the dramatic decrease in neutralizing antibody titers after four months may be one of the causes of early reinfections. Copyright © 2022 by the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey.

7.
American Journal of Transplantation ; 22(Supplement 3):736, 2022.
Article in English | EMBASE | ID: covidwho-2063513

ABSTRACT

Purpose: Kidney transplant recipients (KTR) commonly exhibit inadequate responses to 2-dose COVID-19 vaccination schedules and remain at increased risk of severe COVID-19. Gut dysbiosis is common among KTRs and has been associated with poor vaccine responses. We hypothesised that a dietary fibre supplement may correct dysbiosis and enhance responses to a third dose of COVID-19 vaccine in KTRs. Method(s): KTRs who had received 2 doses of a COVID-19 vaccine were recruited from 2 transplant programs in Australia. KTRs with an inadequate response (defined by anti-RBD <100U/mL) were randomised to receive inulin (fibre) or maltodextran (control), 10g dissolved in 200ml water twice daily for 4 weeks prior to, and 4 weeks after a 3rd vaccine, at which time vaccine response was measured by anti-RBD titre, vaccine-specific B and T cell responses, and changes in the gut microbiome. Patients and investigators were blinded to treatment assignment. COVID-19 infection was excluded by measurement of anti-nucleocapsid antigen. Result(s): Of 85 KTRs screened, 71 had baseline anti-RBD<100U/mL and were randomised to inulin (n=37) or control (n=34). Participants were 33% female, mean age 59 yrs (SD 11), with mean eGFR 56 ml/min/1.73m2 (SD 24.8), and were most commonly receiving tacrolimus, mycophenolate and prednisolone. All participants received a third dose of a mRNA COVID-19 vaccine after receiving a dietary supplement for 4 weeks. Week 8 assessment of vaccine response, supplement tolerability and change in microbiome are ongoing. Four participants tested positive for COVID-19 during the study. Conclusion(s): Gut dysbiosis is one potential contributor to the poor COVID-19 vaccine responses exhibited by KTRs. This trial will determine whether a simple dietary fibre supplement is well tolerated and effective in correcting gut dysbiosis and restoring vaccine responsiveness. Improved vaccine responses are urgently required to better protect KTRs from ongoing morbidity and mortality from COVID-19.

8.
American Journal of Transplantation ; 22(Supplement 3):872-873, 2022.
Article in English | EMBASE | ID: covidwho-2063469

ABSTRACT

Purpose: Humoral response to COVID-19 vaccines is attenuated in many solid organ transplant recipients (SOTRs), necessitating additional primary and booster vaccinations. The omicron variant demonstrates substantial immune evasion, and it is not known if boosters increase neutralizing capacity versus omicron among SOTRs. We therefore investigated SOTR antibody response and neutralization versus variants of concern (VOC) including omicron to a 4th vaccine dose (D4). Method(s): Within a national, prospective observational cohort, 25 SOTRs underwent anti-SARS-CoV-2 spike and receptor binding domain (RBD) IgG testing using the Meso Scale Discovery platform before and 2-4 weeks after D4. Surrogate neutralization (%ACE2 inhibition [%ACE2i], range 0-100% with >20% correlating with live virus neutralization), was measured versus full spike proteins of the ancestral ("vaccine") strain and 5 VOCs including delta and omicron. Change in IgG level and %ACE2i were compared using paired Wilcoxon rank-sum testing. Result(s): Demographics are outlined in Table 1, including median (IQR) age 59 (45- 55) years, 64% kidney recipients, and D4 receipt (60% Moderna, 40% Pfizer) median (IQR) 93 days (28-134) post D3. Two participants had SARS-CoV-2 exposure per anti-nucleocapsid testing, including one incident infection. Overall, anti-RBD (92%- >100%) and anti-spike (84%->92%) seropositivity increased after D4, as did median (IQR) anti-spike IgG 42.3 (4.9-134.2)->228.9 (115.4-655.8) WHO binding antibody units (p<0.05). Median (IQR) %ACE2i significantly increased after D4 vs the vaccine strain 5.8% (0-16.8)->20.6% (5.8-45.9) and delta variant 9.1% (4.9-12.8)->17.1% (10.3-31.7) (both p<0.001). In contrast, no SOTR showed neutralization vs omicron before or after D4: median (IQR) %ACE2i 4.1% (0-6.9)->0.5% (0-5.7) (p=0.11). Conclusion(s): Although a 4th vaccine dose increased anti-spike IgG and neutralizing capacity vs some VOC, there was no omicron variant neutralization among SOTRs. SOTRs may remain at high risk for SARS-CoV-2 infection despite boosting, thus additional protective interventions should be urgently explored. (Figure Presented).

9.
American Journal of Transplantation ; 22(Supplement 3):661-662, 2022.
Article in English | EMBASE | ID: covidwho-2063464

ABSTRACT

Purpose: Transplant volumes decreased significantly during the first months of global pandemic of COVID-19, followed by a shift in the standard of care of transplant medicine. It has become widely accepted to rigorously screen and test donors and recipients for COVID-19 before proceeding with transplant. Discarded kidneys due to positive COVID-19 testing in potential donors is a new challenge for transplant centers. The emerging vaccines and lines of therapy have given us tools that could be utilized to re-balance the shift in practice and maximize organ utilization. Method(s): In this we present two cases of kidney transplantation from a COVID-19 positive deceased donor. The first recipient was a 40-year-old female who has been vaccinated with two doses of mRNA-1273 vaccine five months before transplant. The second patient was a 41-year-old male without a prior COVID-19 vaccine, he had a natural infection with COVID-19 about 10 months prior to transplant, and antibody was positive for anti-nucleocapsid IgG at the time of transplantation. Both recipients had negative SARS-CoV-2 nasopharyngeal swab PCRs prior to transplantation, and both received induction with anti-thymocyte globulin 5mg/ kg. Both recipients received their transplanted kidneys from the same donor, who tested positive by RT-PCR for COVID-19 from a nasopharyngeal swab three days prior to procurement (Roche Cobas Liat PCR, single cycle threshold). On the following day, the donor's bronchial washing was negative. At the day of procure662 Kidney Deceased Donor Selection ment, repeated PCR from a nasopharyngeal swab was negative, and COVID-19 antibody was positive for anti-nucleocapsid IgG (AbbottTM ARCHITECTTM). The donor cause of death was head trauma with a terminal serum creatinine of 0.3mg /dL Chest imaging did not demonstrate COVID-19 pneumonitis. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin as post-exposure prophylaxis. Result(s): Both recipients had an appropriate renal allograft function. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin. Both recipients demonstrated no signs or symptoms of COVID-19 infection during their hospitalization and were instructed to maintain 14 days of COVID-19 exposure precautions post-discharge. At 12 weeks from transplant, both patients had no symptoms of COVID-19 infection. SARS-CoV-2 RNA has been detected in several organs including kidney, but there was no proof of infective virus in extrapulmonary organs. Conclusion(s): These two cases may broaden the scope of accepting organs from COVID-19 positive deceased donors and the use of casirivimab and imdevimab for immediate post-transplant surgery prophylaxis. While we are not sure if the monoclonal antibodies did offer any benefits here, we think that this report may throw the light on its potential use in post-transplant surgery prophylaxis. Further studies are warranted to examine the benefits of such practice.

10.
American Journal of Transplantation ; 22(Supplement 3):709, 2022.
Article in English | EMBASE | ID: covidwho-2063451

ABSTRACT

Purpose: To determine if HLA allo-antibody levels are affected by COVID-19 in renal transplanted patients and to compare the immunoglobulin class and subclass profiles as well as the epitope binding patterns of anti-HLA and anti-SARS-CoV-2 antibodies. Method(s): A cross-sectional study of 46 kidney transplant recipients diagnosed with PCR+ SARS-CoV-2 infection was conducted. Serum samples were collected at the time of infection. For 21 patients, we obtained historical anti-HLA antibody information before COVID-19. Using a single-antigen bead Luminex assay, we determined IgG, IgG1/2/3/4, IgM, and IgA antibodies against Class I and Class II HLA, as well as against five SARS-CoV-2 (Wuhan strain) protein fragments: nucleocapsid, whole spike (S), spike S1, spike S2 and spike receptor binding domain (RBD). Result(s): 26/46 subjects had anti-HLA antibodies of which fourteen had donorspecific anti-HLA antibodies (DSA) compared with 45/46 had anti-SARS-CoV2 antibodies. The majority of DSA were specific to HLA-DQ (10/14), with a dominant IgG/IgG1/IgG3 subclass prevalence. Anti-SARS-CoV-2 antibodies exhibited stronger reactivity towards S and RBD and had increased IgM (38/43, 79%) and IgA (41/42, 85%) prevalence when compared to DSAs (5/14, 35% and 2/14, 14%, p<0.001).Out of 21 patients with pre-COVID-19 data available, calculated panel antibody reactivity (cPRA) levels did not change after COVID-19 in 14 cases (67%);cPRA increased in two cases (10%), both of them with allograft nephrectomy and immunosuppression discontinuation, and decreased in five patients (20%) (from 65.4+/-12.6% before COVID-19, to 29.4+/-33.6% after COVID-19) (Figure 1). Patients with DSA exhibited significantly lower anti-S IgG (9453+/-9945 vs 17975+/-12792;P=0.001), anti-RBD IgM (4464+/-3693 vs 8751+/-6468;P=0.03) and anti-nucleoprotein IgA (998+/-835 vs 5476+/-6895;P=0.001) anti-SARS-CoV2 antibody MFI values than patients without DSA. Conclusion(s): cPRA values did not increase following PCR confirmed COVID-19 diagnosis in renal transplant recipients and those subjects with pre-existing DSA had lower antibody strength directed at SARS-CoV-2 antigens. The lack of increase in alloantibody response is quite remarkable, since over 80% of the patients underwent either significant reduction or withdrawal of mycophenolate mofetil after COVID-19 diagnosis. (Figure Presented).

11.
American Journal of Transplantation ; 22(Supplement 3):775, 2022.
Article in English | EMBASE | ID: covidwho-2063408

ABSTRACT

Purpose: We aimed to investigate the mortality from SARS-CoV-2 in kidney transplant recipients in the Bronx, New York since the beginning of the pandemic Methods: Between March 16, 2020 and November 5, 2021, 453 patients were diagnosed with SARS-CoV-2 infection. 316 were diagnosed by RT-PCR while the remaining 137 tested positive for anti-SARS-CoV-2 nucleocapsid IgG and did not have significant symptoms and had not been previously tested by RT-PCR Results: Of the 316 patients diagnosed by RT-PCR, 214 patients were hospitalized while 102 patients were managed at home as outpatient. 194 (61.3%) were male, median age 61 years old (IQR: 48-69), predominantly Hispanic (56.2%) and African American (29.5%). 75% received a deceased-donor renal transplant, 58% received anti-thymocyte induction. Most patients were on triple immunosuppression (95% on calcineurin inhibitors, 87% on anti-metabolite, and 97% on prednisone). Hypertension was the most common comorbidity followed by diabetes mellitus, heart disease and lung disease. A total of 65 patients (20.5%) died. The mortality rate was 37 % (47/128) in patients diagnosed between March 16 and April 30, 2020. From May 1, 2020 to end of December 2020 mortality rate has significantly decreased to 11% (7/61). Since the beginning of 2021 till November 5, 2021 the mortality rate is 7.7% (10/129). Twenty-seven patients were diagnosed with COVID-19 despite being partially of fully vaccinated (25 fully vaccinated, 2 after one dose of vaccine). 13/27 (48%) were managed at home while 14/27 (52%) were hospitalized and 2 (7%) of them died. Twenty-eight patients received treatment with casirivimab and imdevimab post diagnosis of SARS-CoV-2 starting 2021 and none of those patients have died. Conclusion(s): In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients was higher earlier at the pandemic and has significantly decreased over time. This could be explained by initial exposure of the patients with higher viral load due to lack of personal protection and social distancing. However, since the judicious use of monoclonal antibodies and vaccination, in addition to social distancing protocols and use of facemask, the mortality in kidney transplant recipients has decreased over time.

12.
American Journal of Transplantation ; 22(Supplement 3):350, 2022.
Article in English | EMBASE | ID: covidwho-2063347

ABSTRACT

Purpose: Exosomes are small vesicles which are released by cells into body fluids. We have demonstrated the presence of circulating exosomes with viral antigens in lung transplant recipients (LTxRs) diagnosed with respiratory viral infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection results Covid-19 disease and SARS-CoV2 infection of LTxRs can be severe with poor clinical outcomes. The goal of this single center study is to determine the development of antibody responses specific to SARS-CoV2 in LTxRs, characterize the immune and molecular markers in the circulating exosomes induced and its role in eliciting immunity. Method(s): To determine that antibody responses and induction of circulating exosomes we enrolled LTxRs with SARS-CoV2 infection (n=50), following 2 doses of vaccination (n=100). Exosomes were isolated from plasma by exosome precipitation kit followed by 0.2 micron filtration and size determination by NanoSight300. Exosomes were subjected to transmission electron microscopy for spike (CSP) and nucleocapsid (CNP) antigens. Exosomes were also characterized by western blot for immune and molecular markers (NFkB, CIITA, 20S proteasome, beta catenin and VWF). C57BL/6 mice were immunized with circulating exosomes isolated from LTxRs with infection. Result(s): 78% of SARS-CoV2 infected LTxRs developed antibodies to CSP and CNP as opposed to normal infected individuals. In contrast, only 55% vaccinated LTxRs developed antibodies to SARS-CoV2 spike. Exosomes from SARS-CoV2 infected and vaccinated individuals contained CSP S2, CNP and immune and molecular markers. Transmission electron microscopy also revealed the presence of CSP and CNP on exosomes. C57BL/6 mice immunized with exosomes carrying CSP developed antibodies to SARS-CoV2 spike antigens. Severe inflammation and lung lesions were also demonstrated in the lungs of mice immunized with exosomes carrying CSP. Conclusion(s): In conclusion, we demonstrated that SARS-CoV2 infected and vaccinated LTxRs induced circulating exosomes with SARS-CoV2 CSP. In addition, exosomes contained important immune activating molecules suggesting that the exosomes induced by SARS-CoV2 may have a physiological role in inducing immune responses. Immunization of mice with exosomes from SARS-CoV2 infected and vaccinated LTxRs not only induced SARS-CoV2 spike specific antibody but also resulted in inflammation and lung lesions in the immunized animals.

13.
American Journal of Transplantation ; 22(Supplement 3):597, 2022.
Article in English | EMBASE | ID: covidwho-2063338

ABSTRACT

Purpose: To investigate the effect of mycophenolate mofetil (MMF) on SARSCoV- 2 vaccination response in kidney transplant recipients using the standard immunosuppressive regimen of tacrolimus (TAC) and MMF. Method(s): A randomized controlled trial in immunologically low risk kidney transplant recipients was performed (EudraCT nr.: 2014-001372-66). Patients were randomized to standard TAC/MMF or TAC monotherapy (TACmono) from 9 months onwards, without steroids. Antibody based immune responses to SARS-CoV-2 vaccination (mRNA-1273 or BNT162b2) were investigated in a central laboratory, as part of the RECOVAC Antibody study (EudraCT nr.: 2021-283 001520-18), 4-8 weeks after the second vaccination. Measurement involved the presence of antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 S-protein (IgG anti-RBD antibody) using the Sanquin anti-SARS-CoV-2 RBD IgG ELISA assay. Patients were classified as non-responders (<=50 BAU/mL), low-responders (50-300 BAU/ mL) and responders (>300 BAU/mL). Result(s): Between 2015 and 2018, 79 recipients were randomized to TAC/MMF (n=41) and TACmono (n=38). At the outbreak of the COVID-19 pandemic in early 2020, 67 patients were alive with a functioning graft (TAC/MMF n=35, TACmono n=32). In 27 patients antibody responses could be established: Ten patients were excluded from the analyses due to symptomatic COVID-19 infection and 1 due to a positive nucleocapsid test, possibly from an asymptomatic infection. The rest did not participate in the vaccination study, because of ChAdOx1-S, age >80 years or lack of informed consent. Mean age was 64 (43-75) years, median time after transplantation 4.2 (3.0-6.5) years and eGFR was 53 (36-105) ml/min/1.73m2. TAC trough levels were 6.6 (+/-0.3) mug/L in both groups, and MMF dose was 1000 mg daily (range 500- 2000) in TAC/MMF. Median SARS-CoV-2 Spike S1-specific IgG antibody levels were 37.3 BAU/ml in TAC/MMF (5 non, 7 low, 1 responder) and 715.6 BAU/ml in TACmono (1 non, 6 low, 7 responders, p =0.004, figure 1). Of note is that antibody levels of >1000 BAU/ml, as a presumed threshold for protection against Omicron (B.1.1.529), was reached in 1/13 TAC/MMF and 7/14 TACmono patients (p=0.03). Conclusion(s): In this controlled study mycophenolate mofetil on top of tacrolimus severely hampered serological COVID-19 vaccination response.

14.
Chest ; 162(4):A491, 2022.
Article in English | EMBASE | ID: covidwho-2060608

ABSTRACT

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The SARS-CoV-2 pandemic quickly spread throughout the world after it was first identified in Wuhan, China in 2019. Severe cases of hypoxic respiratory failure have since filled hospitals over the past few years. We present a case of an immunosuppressed patient with persistent respiratory failure from SARS-CoV-2, with a failure to mount antibody response, treated with convalescent plasma. CASE PRESENTATION: We present a 54-year-old female with a past medical history significant for rheumatoid arthritis on immunosuppression with methotrexate, prednisone, sulfasalazine, and rituximab who presented with diarrhea, cough, and shortness of breath. She was unvaccinated and tested positive for COVID-19 pneumonia, which was treated with corticosteroids and Remdesevir. CT thorax revealed diffuse infiltrates (Figure-1). She had progressive hypoxia requiring ICU stay and her course was complicated by inferior wall STEMI, requiring Intra-aortic balloon pump and intubation given worsening hypoxia. She had progressive improvement and was discharged from the hospital on 4 L of supplemental oxygen after a 30-day hospital stay. She presented two days after discharge with cough, fevers and increasing oxygen requirements up to 100% high flow nasal cannula. She was septic and was treated with steroids and antibiotics. She was febrile despite broad spectrum antibiotics. CT thorax demonstrated diffuse infiltrates worsened from the previous and steroid dosing was increased (Figure-2). No obvious source of infection was found, and further evaluation revealed positive Covid-19 RT-PCR. Despite her initial infection occurring two months prior, COVID-19 anti-spike and anti-nucleocapsid antibodies were negative. She was treated with two doses of convalescent plasma and had improvement in her oxygenation, going from 80% high-flow nasal cannula to 6L of supplemental oxygen within two days of administration. DISCUSSION: It's unclear whether immunosuppressed patients with rheumatologic disease are at an increased risk of severe SARS-CoV-2 infection. However, the use of immunosuppressants places patients at risk of an improper immune response to infection. In immunocompetent patients, the typical time to negative SARS-CoV-2 RT-PCR is 3 weeks after positivity (1), and most patients develop antibodies within 2-3 weeks after viral exposure (2). Anti-CD20 monoclonal antibodies like rituximab, commonly used for rheumatologic diseases, can hinder humoral immunity, and impair vaccine response (3). Given our patient's immunosuppressive regimen, we suspect she failed to mount an immune response to COVID-19, resulting in 56 days of infection without an adequate antibody response, successfully treated with convalescent plasma. CONCLUSIONS: Patients with significant immunosuppression regimens may fail to produce antibody responses to SARS-CoV-2, resulting in prolonged infection. Reference #1: Rodríguez-Grande, C., Adán-Jiménez, J., Catalán, P., Alcalá, L., Estévez, A., Muñoz, P., Pérez-Lago, L., de Viedma, D. G., Adán-Jiménez, J., Alcalá, L., Aldámiz, T., Alonso, R., Álvarez, B., Álvarez-Uría, A., Arias, A., Arroyo, L. A., Berenguer, J., Bermúdez, E., Bouza, E., … de la Villa, S. (2021). Inference of active viral replication in cases with sustained positive reverse transcription-PCR results for SARS-CoV-2. Journal of Clinical Microbiology, 59(2). https://doi.org/10.1128/JCM.02277-20 Reference #2: Boechat, J. L., Chora, I., Morais, A., & Delgado, L. (2021). The immune response to SARS-CoV-2 and COVID-19 immunopathology – Current perspectives. In Pulmonology (Vol. 27, Issue 5). https://doi.org/10.1016/j.pulmoe.2021.03.008 Reference #3: Eisenberg, R. A., Jawad, A. F., Boyer, J., Maurer, K., McDonald, K., Prak, E. T. L., & Sullivan, K. E. (2013). Rituximab-treated patients have a poor response to influenza vaccination. Journal of Clinical Immunology, 33(2). https://doi.org/10.1007/s10875-012-9813-x DISCLOSURES No relevant relationships by Issa Makki No relevant relationships by John Parent No relevant relationships by Jay Patel No relevant relationships by Ruchira Sengupta

15.
Journal of Pediatric Gastroenterology and Nutrition ; 75(Supplement 1):S274-S275, 2022.
Article in English | EMBASE | ID: covidwho-2058494

ABSTRACT

Background: The phenomenon known as "Long Covid," (LC) marked by post-infectious symptoms of a wide variety, and typically not associated with initial infectious severity, has the potential to become a tremendous public health burden as infections continue at a high rate. Variations of LC may impact over 80% of patients, with unclear pathogenesis, although many speculate that persistent viral presence in end-organ tissue may drive local changes. We previously published a case report noting persistent SARS-nCoV-2 activity in the cecum of a patient 3 months after initial infection (Arostegui et al, JPGN Reports, 2022). We have sought to expand that finding by assessing additional patients who have undergone endoscopic evaluation for presence of SARS-nCoV-2 nucleocapsid, seeking to expand our understanding of the clinical effects of persistent infection. Method(s): We identified 6 patients with onset of symptoms in the post-SARS-nCoV-2 window, who had undergone EGD/colonoscopy without histopathological diagnosis. New blank slides were cut and sent for staining at Histowiz inc (Brooklyn, NY), with rabbit monoclonal SARS-CoV-2 nucleocapsid antibody (GTX635686, 1:10,000). Resulting slides underwent blinded pathology review to identify positives. Chart review was completed on patients who were identified as positive, including histopathology data from endoscopy, medical history, presentation, laboratory results and clinical course. Result(s): Including our initial report, we have identified 4 female patients ages 11-16 to date. Viral presence was identified in the duodenum and TI, but only in one patient in the colon (cecum). Patients presented for evaluation of a variety of GI manifestations including chronic abdominal pain (100%), nausea and vomiting (50%), loss of appetite (50%), tenesmus (50%), hematochezia (25%) as well as weight loss (50%). Notably, of the 4 patients identified, only 1 had a known history of confirmed SARS-nCoV-2 infection. Endoscopic findings in the intestine were normal with the exception of edema noted in the cecum of two patients. Mucosal biopsies were also positive for notable (if typically felt to be non-pathologic) lymphoid aggregates in the Colon (75%) as well as in the Terminal Ileum (50%). Clinical information is summarized in Table 1. Conclusion(s): Additional identification of persistent SARS-nCoV-2 presence in patients ranging from 3-18 months after symptom onset demonstrates a high likelihood that persistent viral presence contributes to post-infectious symptoms in many patients. Patients demonstrated "red flag" symptoms like nighttime awakening with pain, weight loss, and elevated inflammatory markers or calprotectin, but symptomatically improved over time and with measures targeted at IBS. Our limited sample size prevents determination of typical location of persistent viral activity, but it is notable that symptoms for colonic vs. SI persistence were clinically consistent, with diarrhea in colonic persistence and early satiety/pain characterizing SI persistence. Most notably, we have identified a tendency for persistent infection to occur, potentially explaining at least a subset of persistent IBS-like symptoms associated with GI LC. Further work is necessary to determine exactly the prevalence of this issue, as well as to characterize the natural history of the clinical course, and possible effective therapies. (Table Presented).

16.
Journal of Pediatric Gastroenterology and Nutrition ; 75(Supplement 1):S151-S153, 2022.
Article in English | EMBASE | ID: covidwho-2058337

ABSTRACT

Background: The rapid spread and recurrent infections of SARS-CoV-2 has led to increased use and availability of at-home antigen testing, but widespread testing of antibodies against spike and nucleocapsid to monitor vaccine-induced immunity and exposure to the virus is lacking. Most serological tests require a serum sample from a venous blood draw, increasing risk of exposure to COVID-19 and limiting availability and scalability of testing for many patients. This is especially the case for individuals who are immunocompromised, such as those with inflammatory bowel diseases (IBD), which are frequently on medications that might alter their immune response and impact vulnerability to SARS-CoV-2. Use of easily acquired and stably stored dried fingerstick blood serves a promising specimen source for at-home, remote testing for SARS-CoV-2 antibodies. Aim(s): Validate the use of fingerstick blood (dried and then eluted) versus serum as a specimen for the measurement of quantitative spike and nucleocapsid antibodies to SARS-CoV-2 in a diverse cohort of healthy and immunocompromised patients. Method(s): Patients were consented and enrolled into the Pediatric Gastrointestinal Tissue, Stool, Saliva and Blood Registry prior to having an endoscopic procedure. Five mL of blood was obtained by venipuncture and 10 muL of fingerstick blood was collected and dried on a Neoteryx Mitra device. Blood was eluted from the Neoteryx Mitra samples in 200 muL of dilution buffer (1% BSA, 0.05% Tween-20, 140 mM NaCl, 50 mM Tris (pH 8.0), 0.025% sodium azide) and placed on an orbital shaker at a speed of 500 RPM for 3 h. Paired serum and fingerstick blood eluate specimens were run on the quantitative Roche Elecsys SARS-CoV-2 spike antibody assay and the qualitative Roche Elecsys SARS-CoV-2 nucleocapsid antibody assay. Linear regression were performed on each assay with exclusion of values that were above the upper limit of detection of the assay. Result(s): We observed an excellent correlation in both SARS-CoV-2 antibody assays when comparing fingerstick blood eluates and serum. The linear regression for the nucleocapsid antibody assay had a slope of 15.5, intercept of 4.05, and R2 of 0.92, indicating that a Neoteryx value of 1.00 COI (cut-off index) equates to a serum value of 19.6 COI. The linear regression for the spike assay had a slope of 13.6, intercept of 953, and R2 of 0.95, indicating that a value of 1,000 U/mL from a fingerstick sample equates to a serum value of 14,544 U/mL. Conclusion(s): These data demonstrate that fingerstick blood collected on Neoteryx Mitra devices can be used as a specimen source in Roche Elecsys SARS-CoV-2 antibody assays to calculate the serum levels of spike and nucleocapsid antibodies. This can serve as a platform to remotely and reliably monitor the durability of antibody responses to natural infection with and immunization against SARS-CoV-2 in patients. Chart comparisons of nucleocapsid (top) and spike (bottom) protein antibody levels detected via remote fingerstick collection (Neoteryx, x-axis) and venous blood serum (y-axis).

17.
Swiss Medical Weekly ; 152:29S, 2022.
Article in English | EMBASE | ID: covidwho-2040854

ABSTRACT

Background: Since end Dec. 2021, the Omicron SARS-CoV-2 strains have appeared while previous β,g,α or d strains have disappeared. Methods: Analysis of clinical, humoral, cellular and inflammation responses in known patients from the Clinical Immunology Unit [CIU] after Omicron COVID. Recruitment January 1st to June 30th, 2022. Comparison with data of 54 CIU COVID patients from the first wave [1stW]. Measured parameters: β2microglobulin [β2m], C3, C4, ferritin, ECP, anti Spike1 [S1] for Wuhan and Omicron B1.159, ab anti NCP (nucleocapsids) and neutralizing antibodies [NeuAb], Ab phenotyping, leucocyte repartition, lymphocyte phenotyping. Patients: 118 Omicron infected [OmiP]: M 31%, F 69% (Vac 64%, noVac 36%): 24 previously “Naïve COVID” [NaCOV], 18 noVac with a previous β,g,α or d COVID, 64 Vac with no previous COVID and 12 Vac with a previous COVID. Results: No difference between OmiP and 1stW in the kinetics of response to S1 (Omicron or WT) in the first 6 months. It peaks between 45 to 60 d. Anti-NCP ab peaks at 30 to 45 d and is still present ≥ 5 months. Prior infection and/or vaccination is associated with a 2- 3-fold increase of previously detected anti-S1 Wuhan and anti- S1 Omicron. NaCOV develop ab to S1 Wuhan but in much lesser amounts than 1stW. Among OmiP no increased counts of eosinophils and NK as observed in 1stW, neither any increase in β2m and CRP. The majority of OmiP have elevated serum ECP and increased polyclonal ab production for ≥ 4 months. Conclusions: Omicron induces a different immune response than previous strains of SARS-CoV-2.

18.
HemaSphere ; 6:3924, 2022.
Article in English | EMBASE | ID: covidwho-2032149

ABSTRACT

Background: Patients with hematological malignancies are at a higher risk of developing severe form and protracted course of COVID-19. Remdesivir, an inhibitor of RNA polymerase was identified early as a promising therapeutic regimen for COVID-19, while convalescent plasma (CP) therapy with anti-SARS-CoV-2 antibodies can aid the treatment of COVID-19 in B-cell depleted patients. Aims: Here we investigated whether the combination of externally administered immunoglobulins (Ig) via CP therapy and specific inhibition of viral replication might be sufficient to effectively treat B-cell depleted patients with COVID-19. Methods: We enrolled a series of 20 consecutive patients who suffered from various hematological malignancies with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. These patients demonstrated a profound B-cell lymphopenia based on flow cytometry analysis of peripheral blood lymphocyte subpopulations. Consequently, they showed undetectable baseline anti-SARS-CoV-2 Ig levels before CP therapy according to anti-SARS-CoV-2 nucleocapsid-and S1-RBD-specific total Ig tests. Each patient received a complete course of remdesivir and at least one unit (200 ml) of AB0 compatible convalescent plasma during their treatment for COVID-19. Results: Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of Bcell lymphopenia (p=0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p=0.017), length of hospital stay (p=0.007), and PCR positivity (p=0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p<0.001) and hospital stay (p<0.0001). In those cases where there were at least ten days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p<0.001). Summary/Conclusion: Via combined administration of remdesivir and CP, we experienced an overwhelming survival rate in COVID-19 patients with hematological malignancies. Inhibition of viral replication with passive immunization proved to be efficient and safe. Our results suggest the clear benefit of early administration of CP to avoid protracted COVID-19 disease in patients with B-cell lymphopenia.

19.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009663

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19), caused by betacoronavirus SARS-CoV-2, is associated with an increased risk of severe infection or death in cancer patients compared to the general population. The CANVAX trial recently demonstrated that short term immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer- particularly those who receive myelosuppressive chemotherapy. Because little is known regarding longitudinal antibody or T-cell responses in cancer patients who receive cytotoxic chemotherapy or non-myelosuppressive targeted systemic therapy, the aim of this longitudinal study is to assess immune B and T cell responses to SARS-CoV-2 over a 12-month period in solid tumor patients who receive chemotherapy or non-immunosuppressive therapy compared to healthy individuals without cancer. Methods: This is an ongoing prospective non-interventional clinical trial (NCT05238467). Approximately 100 patients will be enrolled into three different arms. Accrual began in May 2021 and 37 patients have been enrolled. Eligible patients must not have prior COVID-19 infection < 6 months from study enrollment and have a diagnosis of a solid tumor (breast, genitourinary, or gastrointestinal cancers), who either: received myelosuppressive chemotherapy within 60 days prior to initial or booster COVID vaccination, or who started on chemotherapy within 30 to 60 days after the initial or booster COVID vaccination (Arm A);or received non-immunosuppressive treatments (Arm B);or have no history of cancer or prior history of cancer but beyond 12 months from completion of curative cancer treatment (Arm C, control cohort). Whole blood will be collected in accordance with standard operating procedures. Blood samples analyzed for the presence of antibodies against the major antigenic components of SARS-CoV-2 including the spike glycoprotein (S), receptor binding domain (R) and nucleocapsid phosphoprotein (N). Antibody levels will be quantified utilizing quantitative ELISA. T-cell responses will also be quantified. The primary endpoint is seroprotection rate with an antibody titer protective (1:40) at any point: baseline, 2, 6, and 12 months. The secondary endpoint is to evaluate differences in longitudinal immunological responses to SARSCoV- 2 over a 12-month period. The difference of the seroprotection rate among 3 cohorts of participants will be examined using chi-square test. Moreover, the effect of treatment (chemotherapy, endocrine, TKIs) on seroprotection will be estimated using multivariable logistic regression controlling the effects of confounders, such as age, gender and cancer type. COVID antibody titers measured over time (baseline, 8 weeks, 6, 9, 12 months after the second vaccination) will be analyzed using mixedeffect models. .

20.
Annals of the Rheumatic Diseases ; 81:118, 2022.
Article in English | EMBASE | ID: covidwho-2009141

ABSTRACT

Background: Concerns have been raised regarding risks of COVID-19 breakthrough infections in vaccinated patients with immune-mediated infammatory diseases (IMIDs) treated with immunosuppressants, but data on COVID-19 breakthrough infections in these patients are still scarce. Objectives: The primary objective was to compare the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 delta variant between fully vaccinated IMID patients with immunosuppressants, and controls (IMID patients without immunosuppressants and healthy controls). The secondary objective was to explore determinants of breakthrough infections. Methods: In this study we pooled data collected from two large ongoing prospective multi-center cohort studies (Target to-B! [T2B!] study and ARC study). Clinical data were collected between February and December 2021, using digital questionnaires, standardized electronic case record forms and medical files. Post-vaccination serum samples were analyzed for anti-RBD antibodies (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC study only). Logistic regression analyses were used to assess associations with the incidence of breakthrough infections. Multivariable models were adjusted for age, sex, cardiovascular disease, chronic pulmonary disease, obesity and vaccine type. Results: We included 3207 IMID patients with immunosuppressants and 1810 controls (985 IMID patients without immunosuppressants and 825 healthy controls). The incidence of COVID-19 breakthrough infections was comparable between patients with immunosuppressants (5%) and controls (5%). The absence of SARS-CoV-2 IgG antibodies after COVID-19 vaccination was independently associated with an increased incidence of breakthrough infections (P 0.044). The proportion of asymptomatic COVID-19 breakthrough cases that were additionally identifed serologically in the ARC cohort was comparable between IMID patients with immunosuppressants and controls;66 (10%) of 695 patients vs. 64 (10%) of 647 controls. Hospitalization was required in 8 (5%) of 149 IMID patients with immunosuppressants and 5 (6%) of 86 controls with a COVID-19 breakthrough infection. Hospitalized cases were generally older, and had more comorbidities compared with non-hospitalized cases (Table 1). Hospitalization rates were signifcantly higher among IMID patients treated with anti-CD20 therapy compared to IMID patients using any other immunosuppres-sant (3 [23%] of 13 patients vs. 5 [4%] of 128 patients, P 0.041;Table 1). Conclusion: The incidence of COVID-19 breakthrough infections in IMID patients with immunosuppressants was comparable to controls, and infections were mostly mild. Anti-CD20 therapy might increase patients' susceptibility to severe COVID-19 breakthrough infections, but traditional risk factors also continue to have a critical contribution to the disease course of COVID-19. Therefore, we argue that most patients with IMIDs should not necessarily be seen as a risk group for severe COVID-19, and that integrating other risk factors should become standard practice when discussing treatment options, COVID-19 vaccination, and adherence to infection prevention measures with patients.

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